NCI Protocol: S1607 ?A Phase II Study of Combining Tamilogene Laherparpvec (T-VEC) (NSC-785349) and MK-3475 (Pembrolizumab) (NSC-776864) in Patients with Advanced Melanoma Who have Progressed on Anti-PD1/L1 Based Therapy.? Talimogene laherparepvec (T-VEC, formerly known as OncoVEXGM-CSF) is an oncolytic virus based on a modified herpes simplex virus type-1 (HSV-1). It is designed to selectively replicate in tumor tissue and to stimulate local and systemic antitumor immune response. Intralesional administration of talimogene laherparepvec (T-VEC) results in oncolysis of tumor cells and local release of progeny virus as well as of tumor cell antigens. Viral pathogens are strong inducers of interferon responses, and their intratumoral injection results in a change in the tumor microenvironment that is more permissive to a T-cell response. Furthermore, GM-CSF, the product of the viral transgene, is also produced locally to recruit and stimulate antigen-presenting cells. Overall, this strategy is expected to result in the destruction of injected tumors via oncolysis and also uninjected sites of disease (including micro-metastases) via a systemic antitumor immune response. Cohort A (with visceral disease) will use a 2-stage design with an accrual goal of 17 eligible patients in total. This includes 9 eligible patients in the first stage and 8 eligible patients in the second stage. The anticipated accrual rate for Cohort A is 1 patient per month. Assuming an ineligibility rate of 10%, we will accrue 19 total patients (10 patients in the first stage and 9 patients in the second stage) to enroll 17 eligible patients Cohort B (with NO visceral disease) will use a 2-stage design with an accrual goal of 25 eligible patients in total. This includes 16 patients in the first stage and 9 patients in the second stage. Assuming an ineligibility rate of 10%, we will accrue 28 total patients to enroll 25 eligible patients.